Oxygenation of Nonnative Substrates Using a Malfunction State of Cytochrome P450s
The substrate specificity of bacterial cytochrome P450s is very high. Therefore, their catalytic activities toward nonnative substrates are low, whereas their inherent catalytic activities are very high compared with P450s isolated from animals and plants. Using “decoy” molecules, whose structures are very similar to natural substrates, to trick their substrate recognition with decoy molecules, we can induce a malfunction state of cytochrome P450s. Decoy molecule binding under this malfunction state allows bacterial cytochrome P450s to catalyze the oxidation reaction of nonnative substrates. This system using decoy molecules does not require any substitution of amino acids to alter substrate specificity or any changes in the enantioselectivity of nonnative substrate oxidation.
KeywordsBacterial cytochrome P450s Decoy molecules Nonnative substrates Substrate misrecognition Substrate specificity
This work was supported by Grants-in-Aid for Scientific Research (S) to Y.W. (24225004) and a Grant-in-Aid for Young Scientists (A) to O.S. (21685018) from the Ministry of Education, Culture, Sports, Science, and Technology (Japan).
- Bell SG, Stevenson JA, Boyd HD, Campbell S, Riddle AD, Orton EL, Wong LL (2002) Butane and propane oxidation by engineered cytochrome P450(cam). Chem Commun (5):490–491Google Scholar
- Lee DS, Yamada A, Sugimoto H, Matsunaga I, Ogura H, Ichihara K, Adachi S, Park SY, Shiro Y (2003) Substrate recognition and molecular mechanism of fatty acid hydroxylation by cytochrome P450 from Bacillus subtilis. Crystallographic, spectroscopic, and mutational studies. J Biol Chem 278:9761–9767CrossRefPubMedGoogle Scholar
- Matsunaga I, Yamada A, Lee DS, Obayashi E, Fujiwara N, Kobayashi K, Ogura H, Shiro Y (2002b) Enzymatic reaction of hydrogen peroxide-dependent peroxygenase cytochrome P450s: kinetic deuterium isotope effects and analyses by resonance Raman spectroscopy. Biochemistry 41:1886–1892CrossRefPubMedGoogle Scholar